title: Interferon therapy in HCV-positive mixed cryoglobulinaemia: viral and host factors contributing to efficacy of the therapy.
abstract: BACKGROUND
  In a previous paper, we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mixed cryoglobulinaemia.
  
  
  OBJECTIVE
  We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment.
  
  
  METHODS
  In 27 females and 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobulinaemia, bone marrow biopsy and phenotyping of marrow cells were performed before treatment and at the end of follow-up. A liver biopsy was obtained from patients showing biochemical signs of chronic liver disease. The presence of hepatitis C virus was assessed by detection of serum anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The treatment schedule was 3 million units of recombinant interferon alpha-2b three times a week for one year. Follow-up lasted for 1 year after the end of treatment. The response was classified as follows: 1) Complete response: Disappearance of the cryocrit (or reduction of more than 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but reduction of cryocrit of less than 50%. 3) Minor response: Reduction of cryocrit of less than 20% associated with the disappearance of one or more (but not all) signs of vasculitis.
  
  
  RESULTS
  Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RNA was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indicating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6%). After therapy, 13 (31%) patients achieved a complete response, 23 patients (55%) a partial response, and 6 patients (14%) a minor response. Seven of the responders and all patients showing partial or minor responses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found between responders and non-responders/relapsers in terms of age, sex, duration of the disease, severity of symptoms, liver function tests, rheumatoid factor or complement levels, while the lack of response was associated with the presence of genotype 1b, liver cirrhosis, and high cryoglobulin level.
  
  
  CONCLUSIONS
  Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an effective agent for the treatment of this disease and seems able to determine regression of the lymphoproliferative disorder. The hepatitis C virus genotype and cryoglobulin level are the most important predictive factors of response to therapy.
authors.affiliation: First Department of Medicine, Pordenone General Hospital, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Mazzaro
authors.forename: G S
authors.initials: GS
authors.lastname: Carniello
authors.forename: R
authors.initials: R
authors.lastname: Colle
authors.forename: P
authors.initials: P
authors.lastname: Doretto
authors.forename: G
authors.initials: G
authors.lastname: Mazzi
authors.forename: M
authors.initials: M
authors.lastname: Crovatto
authors.forename: G F
authors.initials: GF
authors.lastname: Santini
authors.forename: P
authors.initials: P
authors.lastname: Tulissi
authors.forename: M
authors.initials: M
authors.lastname: Gregoretti
authors.forename: L
authors.initials: L
authors.lastname: Mazzoran
authors.forename: A
authors.initials: A
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Silvestri
authors.forename: G
authors.initials: G
authors.lastname: Pozzato
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D003449:Cryoglobulinemia / Q000150:complications / Q000276:immunology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology* / Q000473:pathology; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D016898:Interferon-alpha; D012367:RNA, Viral